Table 2.
Predicted and observed clearance (mL/min) following drug–drug interactions in children
| Age (years) | Weight (kg) | Observed CL | Predicted CL | Percentage error |
|---|---|---|---|---|
| Theophylline-phenobarbital (effect on theophylline); adult CL = 70 ± 23 mL/min | ||||
| Premature | 2.5 (n = 24) | 1.5 ± 1.1 | 1.3 | − 14 |
| 6–12 | 32 (n = 7) | 53 ± 23 | 38 | − 29 |
| Zidovudine + dideoxyinosine (effect on zidovudine); adult CL = 2505 ± 575 mL/min | ||||
| 3–14 | 35 (n = 8) | 1260 ± 515 | 1489 | 18 |
| Dideoxyinosine + zidovudine (effect on dideoxyinosine); adult CL = 2766 ± 686 mL/min | ||||
| 3–14 | 35 (n = 8) | 2870 ± 1855 | 1645 | 43 |
| Levetiracetam + inducers (carbamazepine, oxcarbazepine, phenobarbital, phenytoin) | ||||
| Adult CL = 107 ± 49 mL/min (effect on levetiracetam) | ||||
| 9.3 | 30 (n = 24) | 100 ± 34 | 57 | − 43 |
| Topiramate-carbamazepine (effect on topiramate); adult CL = 51 ± 11 mL/min | ||||
| < 10 | 30 (n = 4) | 42 ± 9 | 27 | − 36 |
| Topiramate-phenobarbital (effect on topiramate); adult CL = 42 ± 11 mL/min | ||||
| < 10 | 30 (n = 7) | 46 ± 19 | 22 | − 52 |
| 0.9–1.84 | 13 (n = 3) | 17 ± 2 | 8 | − 54 |
| 2–3.7 | 16 (n = 7) | 18 ± 5 | 10 | − 47 |
| Lamotrigine + carbamazepine and phenytoin (effect on lamotrigine) | ||||
| Adult CL of lamotrigine with carbamazepine = 70 ± NA mL/min; with phenytoin = 118 ± NA mL/min | ||||
| < 6 | 15 (n = 3) | 31 ± 11 | 22 | − 29 |
| 7–14 | 37 (n = 4) | 80 ± 27 | 58 | − 28 |
| Lamotrigine + valproic acid (effect on lamotrigine); adult CL = 22 ± 7 mL/min | ||||
| 0.8–2 | 11 (n = 3) | 6.5 ± 3.8 | 3.4 ± 1.0 | − 48 |
| 6–14 | 29 (n = 4) | 13 ± 16 | 11 ± 2.8 | − 15 |
| Digoxin-carvedilol (effect on digoxin); adult CL = 201 ± 34 mL/min | ||||
| 0.08–7.7 | 8 (n = 8) | 20 ± 3 | 23 | 15 |
| Artemether–neviraprine (effect on artemether); adult CL = 33,057 ± NA mL/min | ||||
| 8.3 years | 18 (n = 15) | 10,103 ± NA | 14,502 | 44 |
| Lumefantrine (effect on lumefantrine); adult CL = 35 ± NA mL/min | ||||
| 7.1 | 18 (n = 15) | 9 ± NA | 15 | 67 |
| Etoposide–cyclosporine (effect on etoposide); adult CL = 25 ± 14 mL/min | ||||
| 4.4–9.1 | 40 (n = 6) | 13 ± 4 | 16 ± 5 | 23 |
| 12.1–17 | 50 (n = 6) | 16 ± 7 | 19 ± 7 | 19 |
| 0.83–3.5 | 11 (n = 2) | 7.4 | 4.7 | 36 |
| 14 | 55 (n = 3) | 20 ± 6 | 21 | 4 |
| Cyclosporine–grapefruit (effect on cyclosporine); adult CL = 985 ± 378 mL/min | ||||
| 7–17 | 44 (n = 6) | 1227 ± 120 | 695 | − 43 |
| Vecuronium–phenytoin (effect on vecuronium); adult CL = 561 ± NA mL/min | ||||
| 5–17 | 39 (n = 10) | 589 ± 347 | 362 | − 39 |
| Vecuronium–carbamazepine (effect on vecuronium); adult CL = 630 ± 84 mL/min | ||||
| 4–22 | 43 (n = 10) | 808 ± 563 | 437 | − 46 |
| Mycophenolate mofetil–tacrolimus (IV) [effect on mycophenolate] | ||||
| From a clearance value of 880 ± 360 mL/min from adolescents > 12 to 16 years of age (weight = 60 kg) | ||||
| < 6 | 20 (n = 9) | 550 ± 197 | 386 | − 30 |
| 6–12 | 30 (n = 5) | 725 ± 335 | 523 | − 28 |
| Mycophenolate mofetil–cyclosporine (effect on mycophenolate); adult CL = 181 ± 60 mL/min | ||||
| 5–16 | 50 (n = 0) | 121 ± 36 | 141 | 16 |
| Rifabutin–lopinavir/ritonavir (effect on rifabutin); adult CL = 726 ± NA mL/min | ||||
| 0.83–1.75 | 9 (n = 3) | 109 ± 9 | 93 | − 15 |
| 2.42–3.42 | 12 (n = 3) | 188 ± 87 | 138 | − 27 |
| Sirolimus–cyclosporine (effect on sirolimus); adult CL = 162 ± 73 mL/min | ||||
| 6–11 | 27 (n = 8) | 96 ± 58 | 79 | − 18 |
| 12–18 | 52 (n = 14) | 118 ± 49 | 130 | 10 |
Adult body weight normalized to 70 kg. If the body weights of children were not provided in the article, then the weights were estimated from the body weight chart of the Centers for Disease Control and Prevention (CDC) and from the literature
CL clearance, NA not available, IV intravenous